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Background and PurposeHigh-dose-rate interstitial brachytherapy (HDR-ISBT) is recommended to obtain a better local tumor control for uterine cancer patients in specific situations such as bulky lesions, an extension to the lateral parametrium, or tumors with irregular shapes. Our group uses real-time transrectal ultrasonography (TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to deeply located tumors, but in such cases, repeated image obtainment is required to achieve ideal needle localization. In this report, we present nine cases of patients who underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal and transabdominal ultrasonography (TR/TA-US).Material and MethodsNine uterine cancer patients whose tumors were located deeper than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented. All nine cases had no distal organ metastasis and underwent external beam radiation therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost HDR-ISBT for deeply situated tumors guided by TR/TA-US.ResultsThere were seven cervical cancer and two endometrial cancer patients: six with extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28 months). The average clinical target volume at the time of first HDR-ISBT was 131 ml (range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-ISBT. Another case with carcinosarcoma could not obtain local control and underwent salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases had extra-field recurrence in lymph nodes or distant organs.ConclusionsIn brachytherapy for gynecologic malignancies, deeply situated tumors located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with TR/TA-US.

Highlights • Acute aortic abdominal dissection is a rare complication of retroperitoneal laparoscopic paraaortic lymph node dissection. • Aortic dissection may be part of differential diagnoses in patients with groin and abdominal pain after paraaortic staging. • Uncomplicated type B aortic abdominal dissection should be managed during the subacute phase. • Early contrast-enhanced computed tomography should be performed in case of abdominal pain after paraaortic lymphadenectomy. • Retroperitoneal laparoscopic paraaortic lymph node dissection should be performed at referral cancer centers.

Perirectal hyaluronate gel injection (HGI) appears to be a promising technique for healthy tissue dose sparing in pelvic radiotherapy. In this analysis, we report our initial experience of HGI in gynecologic brachytherapy, focusing on its safety and effectiveness for dose reduction to the rectum. Between July 2013 and May 2014, 36 patients received HGI for primary/salvage gynecologic brachytherapy. Dosimetric effect analysis was based on pre- and post-HGI computed tomography dataset registration with corresponding dose–volume histogram evaluation. The maximum dose to the most exposed 0.1 cm3 (D0.1cm3) and 2.0 cm3 (D2.0cm3) were used as index values for rectum and bladder dose evaluation. The dose indexes for target volume (TV) coverage were TV D90/V100. In all cases, HGI was well tolerated, with no acute or late adverse events documented at a median follow-up of 220 days (range, 18–1046 days). Rectum D2.0cm3 and D0.1cm3 were significantly decreased by HGI (P < 0.001 and P = 0.003, respectively), with no significant impact on dosimetric parameters of bladder and TV coverage. Factors correlating negatively with the dosimetric effect of HGI were an increasing number of interstitial catheters (P = 0.003) as well as Lcranial100% (P = 0.014) and Lcranial80% (P = 0.001) [i.e. the length from the anal verge to the most cranial point at which the 100% and 80% isodose lines, respectively, crossed the rectum]. The concept of HGI for gynecologic brachytherapy is plausible, and our initial experience indicates it to be an effective technique for rectal dose reduction in radiotherapy of intrapelvic tumours.

The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls £ 18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan–Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5–18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0–4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0–18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.

Simple Summary Gynecologic malignancies are those that affect the female reproductive organs, including the ovary, uterus, and cervix. Gynecologic malignancies as a group vary significantly in initial clinical presentation, degree and pattern of spread, and treatment modalities. Our knowledge of the role exosomes play in cancer growth and spread is expanding rapidly. The promise these nanovesicles hold in cancer diagnostics and therapeutics is undeniable, and may be the key to improving the diagnosis and treatment of gynecologic cancers. This paper serves to review laboratory techniques utilized in isolating and studying exosomes, the current state of understanding of exosomes in gynecologic malignancies, and the potential for clinical applications that exosomes may hold. Abstract Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

// Angel Chao 1, 2, * , Chiao-Yun Lin 1, 2, * , An-Ning Chao 3, * , Chia-Lung Tsai 4 , Ming-Yu Chen 1 , Li-Yu Lee 5 , Ting-Chang Chang 1, 2 , Tzu-Hao Wang 1, 2 , Chyong-Huey Lai 1, 2 and Hsin-Shih Wang 1 1 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan 2 Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Kaohsiung, Taiwan 3 Department of Ophthalmology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan 4 Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan 5 Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan * These authors have contributed equally to this work Correspondence to: Tzu-Hao Wang, email: knoxtn@cgmh.org.tw Chyong-Huey Lai, email: sh46erry@ms6.hinet.net Keywords: gynecologic malignancies, LSD1, autophagy, p62 Received: October 25, 2016 Accepted: June 19, 2017 Published: August 10, 2017 ABSTRACT Lysine-specific demethylase 1 (LSD1) – also known as KDM1A – is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 – also termed sequestasome 1 (SQSTM1) – plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

Gynecologic malignancies, including ovarian cancer, endometrial cancer, and cervical cancer, affect hundreds of thousands of women worldwide every year. Wnt signaling, specifically Wnt/β-catenin signaling, has been found to play an essential role in many oncogenic processes in gynecologic malignancies, including tumorigenesis, metastasis, recurrence, and chemotherapy resistance. As such, the Wnt/β-catenin signaling pathway has the potential to be a target for effective treatment, improving patient outcomes. In this review, we discuss the evidence supporting the importance of the Wnt signaling pathways in the development, progression, and treatment of gynecologic malignancies.

Gynecologic cancers cause over 600,000 deaths annually in women worldwide. The development of chemoresistance after initial rounds of chemotherapy contributes to tumor relapse and death due to gynecologic malignancies. In this regard, cancer stem cells (CSCs), a subpopulation of stem cells with the ability to undergo self-renewal and clonal evolution, play a key role in tumor progression and drug resistance. Aldehyde dehydrogenases (ALDH) are a group of enzymes shown to be robust CSC markers in gynecologic and other malignancies. These enzymes also play functional roles in CSCs, including detoxification of aldehydes, scavenging of reactive oxygen species (ROS), and retinoic acid (RA) signaling, making ALDH an attractive therapeutic target in various clinical scenarios. In this review, we discuss the critical roles of the ALDH in driving stemness in different gynecologic malignancies. We review inhibitors of ALDH, both general and isoform-specific, which have been used to target CSCs in gynecologic cancers. Many of these inhibitors have been shown to be effective in preclinical models of gynecologic malignancies, supporting further development in the clinic. Furthermore, ALDH inhibitors, including 673A and CM037, synergize with chemotherapy to reduce tumor growth. Thus, ALDH-targeted therapies hold promise for improving patient outcomes in gynecologic malignancies.

Objective The role of F-18-fluorothymidine (FLT) PET-CT imaging in the evaluation of gynecologic cancers has not been established. We sought to evaluate (FLT) PET-CT imaging in gynecologic cancers by comparing standard uptake values (SUVs) of FLT with F-18-fluorodeoxyglucose (FDG) PET in the primary tumor at diagnosis, and assess FLT uptake immediately following concurrent chemoradiotherapy (chemoRT). Methods In this pilot study, patients treated for cervical (5) or vaginal (1) cancer underwent FLT-PET and FDG-PET scanning at diagnosis (FLT1 and FDG1). Five patients (4 cervical and 1 vaginal) also underwent FLT-PET within 1–3 weeks after chemoRT before brachytherapy (FLT2). Wilcoxon rank-sum test was used to compare the FLT1 and FDG1 parameters. Results Median age at diagnosis was 61-years (range, 33–72). Cervical cancers were staged as IB2 (n = 1, 20%), IIB (n = 1, 20%), IIIB (n = 1, 20%) and IVA (n = 2, 40%) and the single vaginal cancer was staged IIIB. The most common histology was squamous cell carcinoma (n = 3, 50%) followed by adenocarcinoma (n = 2, 33%) and clear-cell adenosquamous carcinoma (n = 1, 17%). Median tumor SUVmax at diagnosis was 7.8 on FLT1-PET (3.9–14.2) versus 11.6 (5.9–23.2) on FDG1-PET (p = 0.15). Tumor SUVmax of FLT declined 54%–100% after chemoRT. Conclusion The tumor SUV of FLT at diagnosis was lower than that of FDG-PET. FLT uptake was markedly decreased after chemoRT. Results indicate that there may not be a significant effect of inflammation on FLT uptake in gynecologic cancers. FLT may be a useful tool when assessing the effects of chemoRT on gynecologic malignancies and planning for postchemoRT brachytherapy treatments., Highlights • Standard uptake values of FLT were compared with FDG-PET in GYN cancer patients. • FLT tracer uptake markedly decreased after chemoradiation therapy (chemoRT). • There may not be a significant effect of inflammation on FLT uptake after RT.

Musikhören kann Körper und Psyche beeinflussen. Ob aber durch Hören von Mozart- oder Entspannungsmusik Aspekte der Lebensqualität während einer so krisenhaften Situation des Beginns einer systemischen zytostatischen Therapie bei Frauen mit gynäkologischen Malignomen positiv beeinflusst werden können, wurde in der vorliegenden Studie erstmals untersucht. Dazu wurden 61 Frauen mit einem Karzinom der Mamma, der Ovarien, der Cervix, des Endometriums oder der Tuben, bei denen eine zytostatische Therapie notwendig war, über den Verlauf der ersten drei Therapiezyklen beobachtet. Es wurden die Stimmung mit Hilfe des Berliner Stimmungsfragebogens (BSF), die Angst durch das State- und Trait-Angst-Inventar von Spielberger, der Stress durch Messung von Tumornekrosefaktor-Alpha (TNF-alpha) mittels ELISA-Technik im Serum, sowie durch ein standardisiertes Tagebuch Übelkeit und Erbrechen sowie die subjektive Qualität des Schlafes und des körperlichen Allgemeinbefindens erhoben und analysiert. 30 Studienpatientinnen hörten regelmässig eine der beiden Studien-CDs (Klaviersonaten von Mozart oder instrumentale Entspannungsmusik von Gomer Edwin Evans), 31 Patientinnen dienten als Kontrollgruppe. Die persönliche Einschätzung des Nutzens des Musikhörens wurde im Rahmen einer abschließenden Beurteilung erfragt. Die Stimmung der Patientinnen der Interventionsgruppe konnte durch das Musikhören positiv beeinflusst werden: die Skalen „Teilnahmslosigkeit“, „gehobene Stimmung“ und „ängstliche Depressivität“ des BSF zeigten einen signifikant positiveren Verlauf als in der Kontrollgruppe. Auf die Aspekte Angst, Stress, Schlaf und körperliches Allgemeinbefinden konnten in der durchgeführten Untersuchung kein Einfluss genommen werden. Zytostatikainduzierte Nausea und Emesis konnten scheinbar durch das Hören der Studienmusik nicht wesentlich beeinflusst werden. Die Akzeptanz des Angebots Musik während der Chemotherapie zu hören war sehr gut, 92% der Patientinnen würden gerne während weiterer Therapiezyklen Musik hören. Fazit: Durch die durchgeführte Untersuchung lässt sich nachweisen, dass Musikhören einen positiven Einfluss auf die Stimmung von Frauen mit gynäkologischen Malignomen während der Chemotherapie haben kann. Eine Reduktion von Angst, Stress oder zytostaikainduzierter Nausea und Emesis konnte in unserer Untersuchung leider nicht nachgewiesen werden. Musikhören wird von den gynäkologisch-onkologischen Patientinnen sehr positiv angenommen und lässt sich unkompliziert in den klinischen Alltag integrieren., Listening to music can influence body and mind. But whether aspects of quality of life during the beginning of a systemic cytostatic chemotherapy of women with gynecologic malignancies can be influenced by listening to Mozart or relaxation music is being investigated in this study for the first time. For this purpose 61 women with a malignant tumor of the breast, the ovaries, the cervix, the endometrium or the tubes, in need of a cytostatic chemotherapy, have been investigated during the first three therapy cycles. Data about mood (via the Berliner Stimmungsfragebogen BSF), anxiety (via the State-Trait- Anxiety-Inventory of Spielberger STAI), stress (via measurement of TNF-alpha) and by means of a standardized diary nausea and emesis, the quality of sleep and the somatic general condition were collected and analyzed. 30 patients of the study listened regularly to one of the two study-cds (piano sonatas by Wolfgang Amadeus Mozart or instrumental relaxation music by Gomer Edwin Evans), 31 patients formed the control group. The personal opinion about the usefulness of listening to the music was given through a final evaluation by the patients of the intervention group at the end of the study. The mood of the patients in the intervention group was influenced positively by listening to music: the scales “unresponsiveness”, “high spirits” and “anxious depressiveness” of the BSF showed a significantly more positive development than in the control group. The aspects anxiety, stress, sleep, nausea and emesis and somatic general condition could not be influenced considerably in this investigation. The acceptance of the offer to listen to music while chemotherapy was very good: 92% said that they would like to listen to music again while a next therapy cycle. Conclusions: By means of the carried out clinical study it can be shown that listening to music can influence the mood of gynecologic cancer patients while chemotherapy positively. A reduction of anxiety, stress or nausea and emesis could not be accomplished. Listening to music is very well accepted by gynecologic-oncological patients and can be integrated very easily into the clinical daily routine.

Während der Zeit der Chemotherapie sehen sich Patienten mit vielfältigen körperlichen, psychischen und sozialen Problemen konfrontiert, die ihre Lebensqualität erheblich einschränken können. Rezeptive Musik ist ein bewährtes, leicht zu implementierendes Medium zur Entspannung, Ablenkung und Verbesserung der Lebensqualität im Krankenhaussetting. Mit vorliegender Studie wurde zum ersten Mal die Wirkung von Musik bei Patientinnen mit gynäkologischen Malignomen während der Chemotherapie untersucht. Dazu wurden prospektiv 61 Patientinnen eingeschlossen, wobei 30 Musik hörten (Mozart- oder Instrumentalmusik) und 31 als Kontrollgruppe dienten. Das Konzept der Studie war leicht durchführbar, was durch die hohe Einwilligungsrate von 86% und die Compliancerate von 77% noch unterstrichen wird. Damit zeigten die Patientinnen unserer Studie eine größere Teilnahmebereitschaft im Vergleich mit anderen Studien. Musikhören hatte keinen positiven Einfluss auf körperliche Beschwerden (gemessen durch den GBB-Fragebogen), Krankheitsverarbeitung (gemessen durch den FKV-Fragebogen), Schlaf, körperliches Befinden, Blutdruck und Puls oder Stress. Es gab allerdings Hinweise auf einen positiven Einfluss von Musik auf das seelische Befinden der Patientinnen. Desweiteren gab es eine Verringerung der Frequenz des Erbrechens in der Musikgruppe. Es bleibt unklar, ob diese Beobachtung als ein Effekt des Musikhörens zu betrachten ist oder durch andere Ursachen, z.B. das Nutzen von Antiemetika erklärt werden kann. Übelkeit war tendenziell, jedoch nicht statistisch signifikant geringer in der Musikgruppe. Die Bewertung der Studie durch die Patientinnen war auβerordentlich positiv. Neunundsechzig Prozent der Patientinnen hatte die Musik gut gefallen, 55% hat sie geholfen sich zu entspannen und 92% gaben an, weiterhin während der Chemotherapie Musik hören zu wollen. Im Vergleich zwischen Mozart- und Instrumentalmusik konnte ein „Mozarteffekt“ nicht bestätigt werden. Die Studie demonstriert das hohe Interesse der Patientinnen an derartigen wissenschaftlichen Untersuchungen und die einfache Integration von rezeptiver Musik in den klinischen Alltag. Sie zeigt, dass Musik einen Beitrag zur Verbesserung der Lebensqualität von Patientinnen während der Chemotherapie leisten kann., During chemotherapy patients are faced with a variety of physical, psychological, and social challenges that can severely limit their quality of life. Receptive music is a proven, easy-to-implement medium for relaxation, distraction, and improving the quality of life in a hospital setting. This study was the first to investigate the effects of music during chemotherapy in patients with gynecological malignancies. Sixty-one patients were enrolled, of which 30 listened to music during therapy (Mozart or instrumental) and 31 served as the control group. The concept of the study was easy to implement, demonstrated by an approval rate of 86% and a compliance rate of 77%. In comparison with other studies the patients showed a greater willingness to participate. Listening to music had no influence on physical complaints (as measured by the GBB questionnaire), coping (as measured by the FKV questionnaire), sleep, physical health, blood pressure and pulse, or stress. However, the study indicates there is a positive influence of music on the mental condition of such patients. Furthermore, there was a reduction in the frequency of vomiting in the music group. It remains unclear whether this can be regarded as an effect of listening to music or is purely a result of other causes, such as the effect of antiemetics. Nausea was slightly, but not significantly lower in the music group. The evaluation of the study by the patients was exceptionally positive. Sixty-nine percent of patients in the music group liked the music, for 55% it had helped them to relax and 92% said they wanted to continue listening to music during chemotherapy. Comparing the effects of Mozart compositions with those of instrumental music did not reveal a “Mozart effect” in this study. The study highlights the willingness of patients to participate in this type of scientific investigation and the ease of integrating receptive music into the everyday clinical practice. Finally, it shows that music can indeed contribute to improving a patient’s quality of life during chemotherapy.

The objective of this article was to review the published scientific literature pertaining to robotic surgery and its applications in gynecologic malignancies and to summarize the impact of robotic surgery on the field of gynecologic oncology. Summarizing data from different gynecologic disease-sites, robotic-assisted surgery is safe, feasible, and demonstrates equivalent histopathologic and oncologic outcomes. In general, benefits to robotic surgery include decreased blood loss, fewer perioperative complications and decreased length of hospital stay. Disadvantages include accessibility to robot surgical systems, decreased haptic sensation and fixed cost as well as cost of disposable equipment. As robotic surgery becomes readily available it will be imperative to develop standardized training modalities. Further research is needed to validate the role of robotic surgery in the treatment of gynecologic malignancies.

Os tumores malignos ginecológicos são uma importante causa de morte por cancro nas mulheres constituindo um problema de saúde pública em todo o mundo e particularmente em Portugal. A radiologia tem um importante papel quer no diagnóstico quer sobretudo na avaliação pré-terapêutica, pelo que se impõe uma uniformização na apreciação destas patologias. O objectivo deste trabalho foi definir os protocolos técnicos de TC e de RM com base na revisão dos consensos europeus recomendados para a abordagem radiológica no estadiamento dos tumores malignos ginecológicos. The gynecological malignancies are an important cause of death from cancer in women and an important public health problem worldwide, particularly in Portugal. Radiology has an essential role both in diagnosis and especially in the pre-therapeutic evaluation, so it imposes uniformity in the assessment of these pathologies. The objective of this study was to define CT and MR imaging technical protocols based on the review of the recommended approach of the european consensus for the radiological staging of gynecological malignancies.